Abstract

IntroductionThe aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).MethodsFlow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.ResultsIncreased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.ConclusionsElevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.

Highlights

  • The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA)

  • We examined the expression of IL-23 receptor (IL-23R) and the chemokine receptors chemokine receptor 4 (CCR4) and Chemokine receptor 6 (CCR6), which influence traffic of these cells into skin and joints

  • Frequency of IL-17+ and IL-22+CD4+ T cells are increased in Peripheral blood mononuclear cell (PBMC) of patients with both PsA and Ps Using flow cytometry, we evaluated intracellular expression of IL-17 and IL-22 and observed a higher proportion of IL17-producing cells within the PBMCs of PsA and Ps patients compared with that of healthy controls (1.0% and 1.1% vs. 0.57%, respectively; P < 0.05, P < 0.01, respectively) (Figure 1A)

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Summary

Introduction

The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA). Ps alone produces significant disability; when combined with PsA, the Whereas recent evidence implicates interleukin 22 (IL22) in the pathogenesis of skin disease in Ps [6,7], PsA has been postulated to more likely involve IL-17 [8,9] Both cytokines can be made by the T helper 17 (Th17) cell subset, but recent reports have described T cells that make IL-22 alone [10,11]. These T cells, subsequently termed Th22 cells, produce IL-22 without IL-17 or interferon γ (IFNγ) and are characterized by the expression of certain chemokine receptors, including chemokine receptor 4 (CCR4) and CCR6, which can influence homing to skin and joints [12]. Genetic studies implicate IL-23 in Ps and PsA [14]

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